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Overcoming clinical relapse in multiple myeloma by understanding and targeting the molecular causes of drug resistance

Objective

Multiple Myeloma (MM) is a currently incurable rare malignant plasma cell disease, which invariably relapses despite therapy. The objective of OVER-MYR is to understand the causes of drug resistance and relapse, develop novel strategies to overcome these, provide proof of principal for phase I/II trial, and thus impact on MM-patient’s survival.Currently-used drugs target both MM cells (MMC) and cells of the bone marrow (BM) microenvironment or ‘niche’ that are critical for supporting MMC survival, proliferation and growth. Since patients repeatedly relapse after such treatments, the following mechanisms of relapse are considered and need to be investigated:
i) drugs have spared specific subclones or subpopulations of MMC
ii) drugs induce alterations in cells of the ‘niche’ that promote drug-resistance.
OVER-MYR integrates a network of outstanding researchers from 6 EU countries with internationally recognized experience in clinics and human and animal models of MM, who will jointly:
WP1: Study the molecular alterations in primary MM and environment cells in samples obtained from a large number of patients at treatment inclusion and relapse, using high throughput techniques.
WP2: Implement in vitro and in vivo models of drug resistance to evaluate molecular and cellular mechanisms and compare their characteristics with drug resistant cells isolated from patients.
Combined results of WP1 and WP2 will permit the identification of 10 prominent (altered) candidate genes involved in MM relapse. Changes in drug resistance, cell survival and proliferation will be assessed in WP2 by modulating the expression of the selected genes.
WP3: Determine how cells from the niche alter their functions in the presence of drugs, and how drug-altered cells impact on MM cells during therapy.
WP4: Screen chemical libraries for drugs active on generated sensitive cell lines, develop innovative inhibitors and provide proof of principle for a phase I/II trial

Field of science

  • /medical and health sciences/basic medicine/pharmacology and pharmacy/drug resistance

Call for proposal

FP7-HEALTH-2011-two-stage
See other projects for this call

Funding Scheme

CP-FP - Small or medium-scale focused research project

Coordinator

VRIJE UNIVERSITEIT BRUSSEL
Address
Pleinlaan 2
1050 Brussel
Belgium
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 431 720
Administrative Contact
Nik Claesen (Mr.)

Participants (9)

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
France
EU contribution
€ 509 953
Address
Rue De Tolbiac 101
75654 Paris
Activity type
Research Organisations
Administrative Contact
Vincent Boyer (Mr.)
UNIVERSITATSKLINIKUM HEIDELBERG
Germany
EU contribution
€ 511 680
Address
Im Neuenheimer Feld 672
69120 Heidelberg
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Thorsten Brietz (Mr.)
UNIVERSITY OF SOUTHAMPTON
United Kingdom
EU contribution
€ 324 564
Address
Highfield
SO17 1BJ Southampton
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Yan Qiao (Ms.)
ACADEMISCH MEDISCH CENTRUM BIJ DE UNIVERSITEIT VAN AMSTERDAM
Netherlands
EU contribution
€ 324 600
Address
Meibergdreef 15
1105AZ Amsterdam
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Frank J.M. Groen (Mr.)
THE GARVAN INSTITUTE OF MEDICAL RESEARCH CHARITABLE INSTITUTION
Australia
EU contribution
€ 324 600
Address
Victoria Street 384
2010 Sydney Nsw
Activity type
Research Organisations
Administrative Contact
Cate Smith (Ms.)
UNIVERSITA DEGLI STUDI DI BARI ALDO MORO
Italy
EU contribution
€ 250 800
Address
Piazza Umberto I 1
70121 Bari
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Vincenzo De Fazio (Dr.)
CELLZOME AG

Participation ended

Germany
Address
Meyerhofstrasse 1
69117 Heidelberg
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Markus Reinhard (Mr.)
INSERM TRANSFERT SA
France
EU contribution
€ 176 988
Address
Rue Watt 7
75013 Paris
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Louis Jammayrac (Mr.)
ONCODESIGN SA
France
EU contribution
€ 144 593
Address
Rue Jean Mazen 20
21000 Dijon
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Jan Hoflack (Dr.)